Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy

Abstract

Purpose of review

Over the last years, evidence is accumulating that enhanced late sodium current (I_NaL) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of I_NaL-induced arrhythmias and the significance of I_NaL-inhibition as a possible therapeutic approach.

Recent Findings

Inhibition of enhanced I_NaL, e.g., by ranolazine, was shown to reverse these effects in different myocardial diseases including heart failure. The antianginal drug ranolazine has already been examined in larger clinical trials with promising antiarrhythmic actions.

Summary

Enhanced I_NaL was found to be present in several cardiac pathologies like ischemia, long QT syndromes, hypertrophic cardiomyopathy, and heart failure. In settings of enhanced I_NaL, a sodium-dependent calcium overload leads to severe impairment of excitation-contraction coupling and therefore has a high proarrhythmogenic potential. Experimental data showed that inhibition of I_NaL has a high antiarrhythmic potential which could be confirmed in further clinical trials.

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